Synovial Fluid Niche Promoted Differentiation of Dental Follicle Mesenchymal Stem Cells Toward Chondrogenesis in Rheumatoid Arthritis

Overview

Journal Arch Rheumatol

Specialty Rheumatology

Date 2022 Aug 11

PMID 35949879

Authors

Deniz Genc

Merve Sezer Kurkcu

Gurkan Yigitturk

Burcu Gunaydin

Hulya Elbe

Akin Aladag

Bekir Col

Emine Figen Tarhan

Affiliations

Soon will be listed here.

Abstract

Objectives: In this study, we aimed to investigate the differentiation potential of dental follicle mesenchymal stem cells (MSCs) in the synovial fluid (SF) niche of early-onset or end-stage rheumatoid arthritis (RA).

Patients And Methods: Between May 2020 and January 2021, six patients (1 male, 5 females; mean age: 57.5±11.2 years; range, 49 to 65 years) who were diagnosed with RA with the indication of SF aspiration were included in the study. The third passage dental follicle stem cells (DFSCs) were cocultured with fresh SF samples of end-stage or early-onset RA patients in micromass culture system for 21 days. SF samples were analyzed for secreted cytokines. Chondrogenic markers (CD49e, CD49f) were analyzed in DFSCs, gene expression analysis was performed for the expressions of Col I, Col II, Aggrecan and Sox-9, and histochemical analysis was performed by staining three-dimensional pellets with anti-collagen II antibody. The neutralization assay was performed with anti-interleukin (IL)-6, anti-interferon-gamma (IFN-g), and anti-IL-1beta(b).

Results: The high levels of IL-1b and IL-6 were observed in end-stage RA patients' SF samples compared to the early-onset patients (p<0.05). The CD49e and CD49f expressions in DFSCs were significantly higher in the SF samples of end-stage RA patients (p<0.05). Also, the Col II, Sox-9 and Aggrecan messenger ribonucleic acid (mRNA) expressions increased in the DFSCs, when cultured with end-stage RA patients' SF samples (p<0.01). Collagen-II expression in histochemical analysis of micromass pellets was higher in the DFSCs cultured with end-stage RA patients' SF samples. The neutralization of IL-6 significantly decreased the CD49e and CD49f expressions (p<0.05).

Conclusion: The high levels of IL-6 in SF niche of end-stage RA patients were found to differentiate DFSCs toward chondrogenesis. Based on these findings, DFSCs can be used as a new cell-based treatment in RA patients for the cartilage damage.

Citing Articles

Extremely low frequency-electromagnetic fields promote chondrogenic differentiation of adipose-derived mesenchymal stem cells through a conventional genetic program.

Zerillo L, Coletta C, Madera J, Grasso G, Tutela A, Vito P Sci Rep. 2024; 14(1):10182.

PMID: 38702382 PMC: 11068729. DOI: 10.1038/s41598-024-60846-5.

Rheumatoid Synovial Fluid and Acidic Extracellular pH Modulate the Immunomodulatory Activity of Urine-Derived Stem Cells.

cehakova M, Ivanisova D, Strecanska M, Plava J, Novakova Z, Nicodemou A Int J Mol Sci. 2023; 24(21).

PMID: 37958839 PMC: 10648750. DOI: 10.3390/ijms242115856.

Comparison of Biological Properties and Clinical Application of Mesenchymal Stem Cells from the Mesoderm and Ectoderm.

Wang Z, Huang M, Zhang Y, Jiang X, Xu L Stem Cells Int. 2023; 2023:4547875.

PMID: 37333060 PMC: 10276766. DOI: 10.1155/2023/4547875.

References

Berebichez-Fridman R, Montero-Olvera P . Sources and Clinical Applications of Mesenchymal Stem Cells: State-of-the-art review. Sultan Qaboos Univ Med J. 2019; 18(3):e264-e277. PMC: 6307657. DOI: 10.18295/squmj.2018.18.03.002. View

Shioda M, Muneta T, Tsuji K, Mizuno M, Komori K, Koga H . TNFα promotes proliferation of human synovial MSCs while maintaining chondrogenic potential. PLoS One. 2017; 12(5):e0177771. PMC: 5461123. DOI: 10.1371/journal.pone.0177771. View

Jagielski M, Wolf J, Marzahn U, Volker A, Lemke M, Meier C . The influence of IL-10 and TNFα on chondrogenesis of human mesenchymal stromal cells in three-dimensional cultures. Int J Mol Sci. 2014; 15(9):15821-44. PMC: 4200793. DOI: 10.3390/ijms150915821. View

Ostrowska M, Maslinski W, Prochorec-Sobieszek M, Nieciecki M, Sudol-Szopinska I . Cartilage and bone damage in rheumatoid arthritis. Reumatologia. 2018; 56(2):111-120. PMC: 5974634. DOI: 10.5114/reum.2018.75523. View

McInnes I, Schett G . The pathogenesis of rheumatoid arthritis. N Engl J Med. 2011; 365(23):2205-19. DOI: 10.1056/NEJMra1004965. View

Iyer S, Cheng G . Role of interleukin 10 transcriptional regulation in inflammation and autoimmune disease. Crit Rev Immunol. 2012; 32(1):23-63. PMC: 3410706. DOI: 10.1615/critrevimmunol.v32.i1.30. View

Brzustewicz E, Bryl E . The role of cytokines in the pathogenesis of rheumatoid arthritis--Practical and potential application of cytokines as biomarkers and targets of personalized therapy. Cytokine. 2015; 76(2):527-536. DOI: 10.1016/j.cyto.2015.08.260. View

Cho H, Lee A, Kim K . The effect of serum types on Chondrogenic differentiation of adipose-derived stem cells. Biomater Res. 2018; 22:6. PMC: 5845156. DOI: 10.1186/s40824-018-0116-z. View

In t Anker P, Noort W, Scherjon S, Kleijburg-van der Keur C, Kruisselbrink A, van Bezooijen R . Mesenchymal stem cells in human second-trimester bone marrow, liver, lung, and spleen exhibit a similar immunophenotype but a heterogeneous multilineage differentiation potential. Haematologica. 2003; 88(8):845-52. View

10.

Genc D, Zibandeh N, Nain E, Gokalp M, Ozen A, Goker M . Dental follicle mesenchymal stem cells down-regulate Th2-mediated immune response in asthmatic patients mononuclear cells. Clin Exp Allergy. 2018; 48(6):663-678. DOI: 10.1111/cea.13126. View

11.

Livak K, Schmittgen T . Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method. Methods. 2002; 25(4):402-8. DOI: 10.1006/meth.2001.1262. View

12.

Guo Q, Wang Y, Xu D, Nossent J, Pavlos N, Xu J . Rheumatoid arthritis: pathological mechanisms and modern pharmacologic therapies. Bone Res. 2018; 6:15. PMC: 5920070. DOI: 10.1038/s41413-018-0016-9. View

13.

Wehling N, Palmer G, Pilapil C, Liu F, Wells J, Muller P . Interleukin-1beta and tumor necrosis factor alpha inhibit chondrogenesis by human mesenchymal stem cells through NF-kappaB-dependent pathways. Arthritis Rheum. 2009; 60(3):801-12. PMC: 2688727. DOI: 10.1002/art.24352. View

14.

Williams R, Khan I, Richardson K, Nelson L, McCarthy H, Analbelsi T . Identification and clonal characterisation of a progenitor cell sub-population in normal human articular cartilage. PLoS One. 2010; 5(10):e13246. PMC: 2954799. DOI: 10.1371/journal.pone.0013246. View

15.

Liu W, Sun Y, He Y, Zhang H, Zheng Y, Yao Y . IL-1β impedes the chondrogenic differentiation of synovial fluid mesenchymal stem cells in the human temporomandibular joint. Int J Mol Med. 2016; 39(2):317-326. PMC: 5358692. DOI: 10.3892/ijmm.2016.2832. View

16.

Zayed M, Schumacher J, Misk N, Dhar M . Effects of pro-inflammatory cytokines on chondrogenesis of equine mesenchymal stromal cells derived from bone marrow or synovial fluid. Vet J. 2016; 217:26-32. DOI: 10.1016/j.tvjl.2016.05.014. View

17.

Kabat M, Bobkov I, Kumar S, Grumet M . Trends in mesenchymal stem cell clinical trials 2004-2018: Is efficacy optimal in a narrow dose range?. Stem Cells Transl Med. 2019; 9(1):17-27. PMC: 6954709. DOI: 10.1002/sctm.19-0202. View

18.

Lopez-Santalla M, Fernandez-Perez R, Garin M . Mesenchymal Stem/Stromal Cells for Rheumatoid Arthritis Treatment: An Update on Clinical Applications. Cells. 2020; 9(8). PMC: 7465092. DOI: 10.3390/cells9081852. View

19.

Aleksander-Konert E, Paduszynski P, Zajdel A, Dzierzewicz Z, Wilczok A . In vitro chondrogenesis of Wharton's jelly mesenchymal stem cells in hyaluronic acid-based hydrogels. Cell Mol Biol Lett. 2017; 21:11. PMC: 5415830. DOI: 10.1186/s11658-016-0016-y. View

20.

Weyand C, Goronzy J . Immunometabolism in early and late stages of rheumatoid arthritis. Nat Rev Rheumatol. 2017; 13(5):291-301. PMC: 6820517. DOI: 10.1038/nrrheum.2017.49. View